Factor Xa inhibitors versus vitamin K antagonist in morbidly obese patients with venous thromboembolism: a systematic review and meta-analysis

Introduction Guidelines have endorsed non-vitamin K antagonist oral anticoagulants (NOACs), consisting of factor Xa inhibitors (xabans) and direct thrombin inhibitors, as the first line of treatment in venous thromboembolism (VTE) and atrial fibrillation. However, morbidly obese patients were under-represented in landmark trials of NOACs. Therefore, this study aimed to systematically review and perform a meta-analysis of studies on xabans versus vitamin K antagonist (VKA) in this high-risk population with VTE. Methods PubMed, Embase, Medline, Cochrane library, and Google Scholar databases were searched to identify studies that compared xabans and VKA in treating morbidly obese patients with VTE. Morbid obesity was defined as body weight ≥ 120 kg or BMI ≥ 40 kg/m2. Outcomes of interest included recurrent VTE, major bleeding, and clinically relevant non-major bleeding (CRNMB). Results Eight studies comprising 30,895 patients were included. A total of 12,755 patients received xabans while 18,140 received VKAs. No significant difference in the odds of recurrent VTE (OR 0.75, 95% CI 0.55–1.01) and CRNMB (OR 0.69, 95% CI 0.44–1.09) was observed between the xabans group and the VKA group. However, the xabans group was associated with lower odds of major bleeding (OR 0.70, 95% CI 0.59–0.83). Conclusion Xabans have lower odds of major bleeding but similar odds of recurrent VTE when compared with VKAs in treating VTE in morbidly obese patients. Large registry analyses or future randomized controlled trials will be helpful in confirming these findings. Supplementary Information The online version contains supplementary material available at 10.1186/s12872-023-03067-4.

Selection process 8 Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process.

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Data collection process 9 Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process.

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Data items 10a List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g. for all measures, time points, analyses), and if not, the methods used to decide which results to collect.

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10b List and define all other variables for which data were sought (e.g. participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information.

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Study risk of bias assessment 11 Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process.

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Effect measures 12 Specify for each outcome the effect measure(s) (e.g. risk ratio, mean difference) used in the synthesis or presentation of results. 6 Synthesis methods 13a Describe the processes used to decide which studies were eligible for each synthesis (e.g. tabulating the study intervention characteristics and comparing against the planned groups for each synthesis (item #5)).

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13b Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions.

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13c Describe any methods used to tabulate or visually display results of individual studies and syntheses. 6 13d Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used.

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13e Describe any methods used to explore possible causes of heterogeneity among study results (e.g. subgroup analysis, meta-regression). 6 13f Describe any sensitivity analyses conducted to assess robustness of the synthesized results. 6 Reporting bias assessment 14 Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases).

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Certainty assessment 15 Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. 5-6

Item # Checklist item
Location where item is reported Study selection 16a Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. Figure 1 16b Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. Figure 1 Study characteristics 17 Cite each included study and present its characteristics. 6, Table 1 Risk of bias in studies 18 Present assessments of risk of bias for each included study. 7, Table S1-S2

Results of individual studies
19 For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots. 20d Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. 7-8, Figure  S2-S3 Reporting biases 21 Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. 7, Table S1-S2 Certainty of evidence 22 Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. 7, Table S2 DISCUSSION Discussion 23a Provide a general interpretation of the results in the context of other evidence. 8-9 23b Discuss any limitations of the evidence included in the review. 10-11 23c Discuss any limitations of the review processes used. 10-11 23d Discuss implications of the results for practice, policy, and future research. 9-10

OTHER INFORMATION
Registration and protocol 24a Provide registration information for the review, including register name and registration number, or state that the review was not registered. 5 24b Indicate where the review protocol can be accessed, or state that a protocol was not prepared. 5 24c Describe and explain any amendments to information provided at registration or in the protocol. 5 Support 25 Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. 14 Competing interests 26 Declare any competing interests of review authors. 14 Availability of data, code and other materials 27 Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review.